Overactive bladder is a common problem in older women. One factor that might contribute to this problem is an age-related change in adrenergic receptor-mediated control of contractility of the bladder detrusor muscle. With aging, animal studies have shown that adrenergic facilitation of detrusor contractility increases, which may be due indirectly to loss of ovarian hormones. Accordingly, the studies proposed in Specific Aims on urethane-anesthetized female rats are designed to test the hypothesis that depletion of ovarian hormones, such as that which occurs after ovariectomy (OVX) or in aged rats increases the sensitivity or expression of alpha1-adrenergic receptors in the bladder, but has little or no effect on alpha2-adrenergic receptors. To test this hypothesis, the contractile response of the detrusor muscle to alpha1-receptor ligands injected via the bladder blood supply will be compared in urethane-anesthetized rats in the following groups: young rats, OVX rats with and without estrogen replacement, and aged rats. Next, inhibition of nerve-stimulation induced bladder contractions by an alpha1-receptor antagonist and facilitation of these contractions by an alpha2-adrenergic agonist will be compared across the same groups. Overall, it is hoped that the results of the studies in this RO3 application will contribute to our understanding of the mechanisms underlying overactive bladder problems in older women and therefore towards improving treatment. The results of these studies will be the basis for developing a longer research program.